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Biomedical subjects

M Palacios

Publications and source records attributed to M Palacios.

At least 19 recordsLinked to original sources

Bifid mandibular condyle: archaeological case report of a rare anomaly.

In this paper, an archaeological case of unilateral bifid mandibular condyle is presented. This uncommon anomaly is characterized by a division of the mandibular condylar head. In this case, the left condyle was divided into two articulating surfaces oriented mediolaterally; two articular facets on the anterior wall of the glenoid fossa for the double condyle were observed. The morphological and radiological analysis do not show any evidence of injuries or degenerative pathology. Taking into account the two main causes of bifid condyle suggested in the literature (traumatic and developmental), an embryopathy by teratogenic agents is proposed as a possible aetiology of the bifid condyle reported here.

History, Ancient↗

Methodologies for estimating disaggregated anthropogenic emissions--application to a coastal Mediterranean region of Spain.

Regional estimates of both anthropogenic and biogenic emissions are important inputs for models of atmospheric chemistry. A disaggregated emissions inventory of all relevant pollutants for an area of 100 x 100 km2 centered in Burriana (Castellon, Spain) has been worked out. Time and spatial resolutions were hourly and 1 x 1 km2, respectively. Estimates were made for all relevant sources of anthropogenic emissions. The pollutants considered were SO2, NOx, NMVOCs (nonmethane volatile organic compounds), CH4, CO, CO2, N2O, and NH3. Thus, the emissions inventory includes up to 18 different NMVOCs. Emissions were computed for a typical sunny workday in June when strong photochemical activity could be expected. A "top-down" methodology was applied, taking as a starting point official annual and provincial estimates based on CORINAIR emission factors. This procedure is a very useful tool, particularly for those cases where a lack of sufficient local detailed information about the main emission-generating activities, such as road traffic, makes the use of a "bottom-up" approximation inadvisable. Moreover, updating these emission inventories is easier and they could be used to evaluate the impact of possible abatement strategies.

Air Pollutants↗

[The inflammatory process of cardiovascular disease: new markers].

For many years the classic model used for explaining the genesis of atheromatosis was that involving classic cardiovascular risk factors, caused either by a harmful life style or by hereditary alterations of the metabolism, principally dislipaemias. Recently we have learnt that, intimate molecular processes, as the inflammatory cytokine and cellular cascades, explain a great part of the vascular damage leading to the ischaemic episodes observed in the clinic. It can even be assessed, in general, the seric inflammation markers, as hypothetical tools for early diagnosis of vascular disease, are located on the physiopathological path between the classic risk factor (arterial hypertension, hypercholesterolaemia, obesity, diabetes) and the arterial lesion. This paper describes these inflammatory mechanisms, both from the viewpoint of basic science and from the viewpoint of its clinical role, and it also analyses the epidemiological value that these might have in the study of populations.

English Abstract↗

Pulmonary inflammation induced by a recombinant Brugia malayi gamma-glutamyl transpeptidase homolog: involvement of humoral autoimmune responses.

BACKGROUND: A major allergen from the lymphatic filarial parasite Brugia malayi implicated in the pathogenesis of tropical pulmonary eosinophilia (TPE) has recently been cloned and identified as the homolog of the membrane-bound mammalian enzyme gamma-glutamyl transpeptidase (gamma-GT). Patients with acute TPE show autoreactive antibodies against endogenous gamma-GT from the pulmonary epithelium. MATERIALS AND METHODS: Recombinant B. malayi gamma-GT, alone or adsorbed to aluminium hydroxide (AL), was used in a BALB/c mouse model to analyze its antigenic/allergenic potential, its potential to induce pulmonary inflammation, and its capacity to induce autoreacting antibodies. RESULTS: Mice immunized with B. malayi gamma-GT showed significant levels of gamma-GT-specific IgG1, IgG2a, IgG3, IgA, IgE antibodies, and mild blood eosinophilia, even in the absence of adjuvant. Intranasal challenge with B. malayi gamma-GT induced peribronchial and perivascular inflammation characterized by a mixed infiltrate of lymphocytes, neutrophils, eosinophils, and macrophages. Both IL-4 and IFN-gamma were detected in the peripheral blood and in the bronchoalveolar lavage fluid of immunized and intranasally challenged mice. Histological analysis of murine lungs using affinity-purified antibodies from mice immunized with the parasite's gamma-GT revealed the presence of autoimmune antibodies against pulmonary epithelium. Western blot analysis identified the 55 kDa heavy chain subunit of the murine gamma-GT as the target of autoreactive/crossreacting antibodies. CONCLUSION: Our data from the in vivo mouse model demonstrate the potent allergenicity/antigenicity of B. malayi gamma-GT, and its capacity to induce pulmonary inflammation upon intranasal challenge. This leads to breakdown of tolerance against endogenous murine gamma-GT. Thus, humoral autoimmunity against the airways epithelium may contribute to the pathogenesis of TPE.

Animals↗

Acute systemic inflammation impairs endothelium-dependent dilatation in humans.

BACKGROUND: We tested the hypothesis that endothelial dysfunction underlies the association between an acute inflammatory episode and the transiently increased risk of a cardiovascular event by examining the effects of an experimental inflammatory stimulus on endothelium-dependent vasodilation. METHODS AND RESULTS: Salmonella typhi vaccine was used to generate a systemic inflammatory response in healthy volunteers. In 12 subjects, dilatation of the brachial artery to flow and to sublingual nitroglycerin (NTG) was recorded (conduit vessel response), and in 6 subjects, venous occlusion plethysmography was used to measure forearm blood flow during intrabrachial infusion of the endothelium-dependent dilators acetylcholine (ACh) and bradykinin (BK) and the endothelium-independent dilators NTG and verapamil (resistance vessel response). Responses were assessed 16 hours before and 8 and 32 hours after vaccination. Vaccination resulted in elevations in white cell count and serum levels of interleukin-6 and interleukin-1 receptor antagonist. Eight hours after vaccination, resistance vessel responses to BK (P:=0.0099) and ACh (P:=0.0414) were markedly attenuated, and brachial artery flow-mediated dilatation was depressed. Resistance vessel responses to verapamil and NTG were unchanged, as was the conduit vessel response to NTG. Thirty-two hours after vaccination, resistance vessel responses to BK and ACh had returned to normal. CONCLUSIONS: S typhi vaccine generates a mild inflammatory reaction associated with temporary but profound dysfunction of the arterial endothelium in both resistance and conduit vessels to both physical and pharmacological dilator stimuli. This finding might explain the association between infection and inflammation and the enhanced risk of an acute cardiovascular event.

Acetylcholine↗

A stability-indicating HPLC method to determine cyproterone acetate in tablet formulations.

A simple and accurate liquid chromatographic method was developed to estimate cyproterone acetate (CA) in pharmaceuticals. The drug was chromatographed on a reversed-phase C18 column. Eluents were monitored at a wavelength of 254 nm utilizing a mixture (60:40) of acetonitrile and water. Solution concentrations were measured on a weight basis to avoid the use of an internal standard. The method was statistically validated for linearity, accuracy, precision, and selectivity. Due to its simplicity and accuracy, we believe that the method can be used for routine quality control analysis. No specific sample preparation is required except for the use of a column guard and a suitable prefilter attached to the syringe.

Androgen Antagonists↗

Outbreak of a multiresistant Klebsiella pneumoniae strain in an intensive care unit: antibiotic use as risk factor for colonization and infection.

An observational study was undertaken to describe a nosocomial outbreak caused by multiresistant Klebsiella pneumoniae (MRKP). Ten patients in the pediatric intensive care unit (ICU) at a hospital in Madrid were colonized by or infected with MRKP from October 1997 to April 1998. Thirty-two patients with MRKP-negative surveillance cultures who were admitted to the ICU during the outbreak period were selected as control patients. Random amplified polymorphic DNA analysis of MRKP isolates revealed patterns that were indistinguishable from each other. After identification of colonized patients by surveillance cultures and implementation of standard and contact precautions, the outbreak was controlled. An age <12 weeks (odds ratio [OR], 13.1) and previous treatment with third-generation cephalosporins and aminoglycosides (OR, 31.2) were independently associated with MRKP colonization and/or infection. Individual exposure to antibiotics, irrespective of other clinical determinants, is a risk factor for MRKP acquisition. Screening high-risk patients during outbreaks and reducing the use of third-generation cephalosporins and aminoglycosides contribute to the control of these epidemics.

Anti-Bacterial Agents↗

Comparison of two different methods for measurement of phenylalanine in dried blood spots.

Phenylketonuria is an inherited metabolic disorder caused by a defect in the hydroxylation of phenylalanine. Newborn screening is crucial for the diagnosis and treatment of this disease. A phenylalanine dehydrogenase-coupled enzymatic assay (Quantase) in microtiter plates for the screening of phenylketonuria was evaluated and compared with our routine method based on the modified fluorometric McCaman method. The test exhibited a linear calibration curve with a good slope as well as sufficient imprecision (< 10%), recovery (99.23+/-4.86%) and limit of detection (54.5 micromol/l). One hundred and ninety dried blood spots were analysed by this enzymatic method and compared with McCaman's. Although Quantase (Teknovas, Bilbao, Spain) showed a phenylalanine mean level in dried blood spot 18.2 micromol/l higher than that obtained with our routine method, the agreement between both techniques was considered acceptable.

Amino Acid Oxidoreductases↗

Cytokine-induced venodilatation in humans in vivo: eNOS masquerading as iNOS.

OBJECTIVE: Venodilatation is a feature of endotoxaemia and sepsis. We have tested directly the hypothesis that three cytokines (IL-1 beta, TNF alpha and IL-6) generated during endotoxaemia affect venous tone in humans in vivo by increasing NO generation and explored whether the NO comes from the iNOS or eNOS isoform. DESIGN AND INTERVENTION: Cytokines were given into a superficial vein in very low doses sufficient only to produce changes in the study vessel. The effects of cytokines on the response to noradrenaline were examined. RESULTS: IL-1 beta increased basal NO-induced dilatation in the study vein, and this was sufficient to attenuate the constrictor response to exogenous noradrenaline or sympathetic stimulation. The effects were maximal at 6 h and both NG-monomethyl-L-arginine and aminoguanidine caused significant reversal of the IL-1 beta effects. However, no induction of iNOS mRNA was detected in the tissue samples. Instead, mRNA encoding eNOS and GTP cyclohydrolase-1 was detected in all vessels. CONCLUSION: The simplest explanation of these results is that IL-1 beta induces expression of GTP cyclohydrolase-1 which leads to increased generation of BH4 and activation of eNOS. This study identifies IL-1 beta as a key cytokine causing physiologically significant venodilatation in humans by increasing NO generation and suggests that this can occur even in the absence of iNOS expression.

Adult↗

Fluoxetine versus amitriptyline in the treatment of major depression with associated anxiety (anxious depression): a double-blind comparison.

Although common in clinical settings, major depressive disorder with associated anxious symptoms ('anxious depression') has not been well studied in antidepressant clinical trials. The aim of this study was to compare the effects of fluoxetine versus amitriptyline in this group of patients. After a single-blind placebo run-in period of 2 weeks, patients were treated on a double-blind basis with fluoxetine or amitriptyline for 8 weeks. Assessment instruments included: 21-item Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Clinical Global Impressions, Raskin Depression Scale and Covi Anxiety Scale. A total of 157 patients were randomized to either fluoxetine or amitriptyline. Fluoxetine was given at a fixed dose of 20 mg/day and amitriptyline was given in a range of 50-250 mg/day (mean of 138.1 mg/day). Fluoxetine was comparable to amitriptyline in all efficacy measures except the HAMD sleep factor. Unwanted effects were more frequent and more severe in the amitriptyline-treated patients. Fluoxetine was comparably efficacious to amitriptyline in the treatment of major depression with associated anxiety. Since fluoxetine was far better tolerated, it is a promising alternative for this frequent and disabling condition.

Adult↗

Prevalence of diabetes mellitus and associated cardiovascular risk factors in an adult urban population in Paraguay.

A cross-sectional study was conducted on a 20-74-year-old population in an urban white-Hispanic population in Paraguay to determine the prevalence of diabetes mellitus (DM), impaired glucose tolerance (IGT), and associated cardiovascular disease (CVD) risk factors. In total 1606 subjects completed the study (response rate 80.3%; 1094 women, 512 men). The overall prevalences were: DM 6.5%, IGT 11.3%, hypertension 17.1%, and obesity 31.6% with more obesity in women (35.7% vs 22.8%, p < 0.05). Age-standardized prevalences were: DM 6.5%, IGT 13.5% in females and DM 5.5%, IGT 7.2% in males. DM and IGT subjects had two or more CV risk factors significantly more often than the normal population. In conclusion, DM, IGT, hypertension, and obesity are common in this South American Hispanic urban population, particularly in women. Public health measures, such as lifestyle education, are required to decrease these noncommunicable diseases.

Adult↗

Ca(2+)-independent nitric oxide synthase activity in human lung after cardiopulmonary bypass.

BACKGROUND: Because surgery involving cardiopulmonary bypass induces a systemic inflammatory response, the effect of cardiopulmonary bypass on nitric oxide (NO) generation was investigated in human lung tissue. METHODS: Nitric oxide synthase (NOS) activity was measured by the conversion of 14C-L-arginine to 14C-L-citrulline in tissue biopsy samples obtained before and after cardiopulmonary bypass. RESULTS: The Ca(2+)-independent production of NO found before cardiopulmonary bypass was extremely low (1.5 (0.5) pmol citrulline/mg/min), but was increased after the bypass operation (23.6 (11) pmol/mg/min). CONCLUSIONS: Ca(2+)-independent NOS activity was detected in human lung after cardiopulmonary bypass. This finding may provide an important insight into the pathogenesis of the tissue damage and acute phase response observed after such surgery.

Amino Acid Oxidoreductases↗

Sperm-egg recognition in the mouse: characterization of sp56, a sperm protein having specific affinity for ZP3.

Recognition between mammalian gametes occurs when the plasma membrane of the sperm head binds to the zona pellucida (ZP), an extracellular coat surrounding eggs. ZP3, one of three glycoproteins in the ZP, is the egg protein recognized by sperm. A mouse sperm surface protein, sp56 (M(r) = 56,000), has been identified on the basis of its specific affinity for ZP3 (Bleil, J. D., and P. M. Wassarman. 1990. Proc. Natl. Acad. Sci. USA. 87:5563-5567). Studies presented here were designed to characterize mouse sperm sp56 and to further test whether or not this protein specifically recognizes ZP3. sp56 was purified by both ZP3 affinity chromatography and by ion exchange chromatography followed by size-exclusion chromatography. The purified native protein eluted from size-exclusion columns as a homomultimer (M(r) approximately 110,000). Each monomer of the protein contains intramolecular disulfide bonds, consistent with its extracellular location. Immunohistochemical and immunoblotting studies, using monoclonal antibodies, demonstrated that sp56 is a peripheral membrane protein located on the outer surface of the sperm head plasma membrane, precisely where sperm bind ZP3. Results of crosslinking experiments demonstrated that the ZP3 oligosaccharide recognized by sperm has specific affinity for sp56. Collectively, these results suggest that sp56 may be the sperm protein responsible for sperm-egg recognition in the mouse.

Amino Acid Sequence↗

Monocyte chemotactic protein-1 inhibits the induction of nitric oxide synthase in J774 cells.

We evaluated the effect of monocyte chemotactic protein-1 (MCP-1) on the induction of nitric oxide synthase activity in J774 cells. MCP-1 was able to inhibit the production of nitric oxide induced by LPS and IFN-gamma in a dose-dependent manner. Moreover, the inhibition was only achieved when the cells were pretreated with MCP-1. No inhibition was observed when MCP-1 was added after stimulation with LPS and IFN-gamma. These results demonstrate that MCP-1 is able to inhibit the induction of nitric oxide synthesis.

Amino Acid Oxidoreductases↗

Chlorpromazine inhibits both the constitutive nitric oxide synthase and the induction of nitric oxide synthase after LPS challenge.

The effects of chlorpromazine on either the activity of mouse brain nitric oxide synthase or the induction of lung nitric oxide synthase in mice and rats were studied. Chlorpromazine inhibited the nitric oxide synthase activity in mouse brain cytosol. This effect could be reversed by adding an excess of calmodulin. In addition, chlorpromazine was able to inhibit the induction of lung nitric oxide synthase, in both species, after LPS administration. Furthermore, chlorpromazine also inhibited arginase activity in mouse lung cytosol.

Amino Acid Oxidoreductases↗

Role of nitric oxide pathway in the protection against lethal endotoxemia afforded by low doses of lipopolysaccharide.

Survival after lipopolysaccharide challenge (LD80, 20 mg.kg-1, i.p.) was significantly enhanced by previous treatment with a microdose of LPS (50 micrograms.kg-1, i.v.). When NG-monomethyl-L-arginine, a specific inhibitor of the formation of nitric oxide from L-arginine, was given 30 minutes before microdose, survival was significantly reduced. When we monitored the serum Tumor Necrosis Factor (TNF) levels in both groups a significant reduction of TNF level after the microdose was observed in mice previously treated with L-NMMA. The ability of L-NNMA to reduce TNF release was dose dependent.

Animals↗